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Identification of a Genomic Region between SLC29A1 and HSP90AB1 Associated with Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance)

Overview of attention for article published in Clinical Cancer Research, June 2018
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5 tweeters

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1 Dimensions

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Title
Identification of a Genomic Region between SLC29A1 and HSP90AB1 Associated with Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance)
Published in
Clinical Cancer Research, June 2018
DOI 10.1158/1078-0432.ccr-17-1523
Pubmed ID
Authors

Megan Li, Flora Mulkey, Chen Jiang, Bert H. O’Neil, Bryan P. Schneider, Fei Shen, Paula N. Friedman, Yukihide Momozawa, Michiaki Kubo, Donna Niedzwiecki, Howard S. Hochster, Heinz-Josef Lenz, James N. Atkins, Hope S. Rugo, Susan Halabi, William Kevin Kelly, Howard L. McLeod, Federico Innocenti, Mark J. Ratain, Alan P. Venook, Kouros Owzar, Deanna L. Kroetz

Abstract

Bevacizumab is a VEGF-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of multiple cancers. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy or lead to cardiovascular complications. The factors that contribute to interindividual variability in blood pressure rise during bevacizumab treatment are not well understood. To identify genomic regions associated with bevacizumab-induced hypertension risk, sequencing of candidate genes and flanking regulatory regions was performed on 61 bevacizumab-treated patients (19 cases developed early-onset grade 3 hypertension and 42 controls had no reported hypertension in the first six cycles of treatment). SNP-based tests for common variant associations and gene-based tests for rare variant associations were performed in 174 candidate genes. Four common variants in independent linkage disequilibrium blocks between SLC29A1 and HSP90AB1 were among the top associations. Validation in larger bevacizumab-treated cohorts supported association between rs9381299 with early grade 3+ hypertension (P = 0.01, OR 2.4) and systolic blood pressure > 180 mmHg (P = 0.02, OR 2.1). rs834576 was associated with early grade 3+ hypertension in CALGB 40502 (P = 0.03, OR 2.9). These SNP regions are enriched for regulatory elements that may potentially increase gene expression. In vitro overexpression of SLC29A1 in human endothelial cells disrupted adenosine signaling and reduced nitric oxide levels that were further lowered upon bevacizumab exposure. The genomic region between SLC29A1 and HSP90AB1 and its role in regulating adenosine signaling are key targets for further investigation into the pathogenesis of bevacizumab-induced hypertension.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 23%
Student > Master 2 15%
Researcher 2 15%
Student > Doctoral Student 2 15%
Unspecified 2 15%
Other 2 15%
Readers by discipline Count As %
Medicine and Dentistry 4 31%
Biochemistry, Genetics and Molecular Biology 4 31%
Unspecified 2 15%
Neuroscience 2 15%
Pharmacology, Toxicology and Pharmaceutical Science 1 8%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 October 2018.
All research outputs
#7,653,234
of 13,583,786 outputs
Outputs from Clinical Cancer Research
#6,779
of 9,641 outputs
Outputs of similar age
#133,230
of 269,647 outputs
Outputs of similar age from Clinical Cancer Research
#50
of 82 outputs
Altmetric has tracked 13,583,786 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,641 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.7. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 269,647 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 82 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.